Cyclodextrin based artificial enzymes

Using cyclodextrins (CDs) as scaffolds for artificial enzymes has emerged as a promising strategy for improving catalytic processes. Due to their less hydrophilic internal environment encapsulation of substrates, the complexes can enhance the concentration of molecules with poor aqueous solubility and facilitate enzymatic-like reactions. However, while involving CDs in enzymatic reactions has shown some success, their catalytic efficiency often falls short of expectations compared to natural enzymes. This discrepancy is primarily due to the inherent limitations of the CD-based systems, such as complex substrate and product stability constants or geometric factors that affect intermolecular interactions. Despite these challenges, CDs are still widely used in the design of artificial enzymes and in understanding the enzymatic reaction mechanisms, especially in applications that require the modification of substrate solubility or the stabilization of reaction intermediates. To overcome the current limitations, future research should focus on optimizing CD modifications or coupling CDs to natural enzymes to enhance their catalytic performance. This review summarizes the CD-based artificial enzyme development, discusses key challenges and limitations of syntheses, and explores potential strategies to improve their catalytic activity. • Cyclodextrin derivatives as scaffolds for artificial enzymes. • Cyclodextrin inclusion complexes act as carriers for hydrophobic substrates. • Inclusion complexes can stabilize reaction intermediates. • The combination of cyclodextrins with natural enzymes can improve catalytic performance. • Equimolar or excess cyclodextrin derivatives limit large scale applications.